Genetic Variant MTF1:c.*5006A>G (chr1-37810130-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005955.3(MTF1):c.*5006A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.683 in 152,194 control chromosomes in the GnomAD database, including 35,466 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.68 ( 35420 hom., cov: 32)

Exomes 𝑓: 0.78 ( 46 hom. )

Consequence

MTF1
NM_005955.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.545

Publications

17 publications found

Variant links:

Genes affected

MTF1 (HGNC:7428): (metal regulatory transcription factor 1) This gene encodes a transcription factor that induces expression of metallothioneins and other genes involved in metal homeostasis in response to heavy metals such as cadmium, zinc, copper, and silver. The protein is a nucleocytoplasmic shuttling protein that accumulates in the nucleus upon heavy metal exposure and binds to promoters containing a metal-responsive element (MRE). [provided by RefSeq, Jul 2008]

MTF1 Gene-Disease associations (from GenCC):

intellectual disability
Inheritance: AD Classification: LIMITED Submitted by: G2P

MTF1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.709 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
MTF1	NM_005955.3 link	c.*5006A>G	3_prime_UTR_variant	Exon 11 of 11	ENST00000373036.5	NP_005946.2
MTF1	XM_011541491.3 link	c.*5006A>G	3_prime_UTR_variant	Exon 11 of 11		XP_011539793.1
MTF1	XM_047421170.1 link	c.*5006A>G	3_prime_UTR_variant	Exon 12 of 12		XP_047277126.1
MTF1	XM_047421173.1 link	c.*5006A>G	3_prime_UTR_variant	Exon 10 of 10		XP_047277129.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTF1	ENST00000373036.5 link	c.*5006A>G		3_prime_UTR_variant	Exon 11 of 11	1	NM_005955.3	ENSP00000362127.3

Frequencies

GnomAD3 genomes

AF:

0.683

AC:

103755

AN:

151928

Hom.:

35372

Cov.:

show subpopulations

Gnomad AFR

AF:

0.679

Gnomad AMI

AF:

0.381

Gnomad AMR

AF:

0.631

Gnomad ASJ

AF:

0.671

Gnomad EAS

AF:

0.728

Gnomad SAS

AF:

0.631

Gnomad FIN

AF:

0.776

Gnomad MID

AF:

0.623

Gnomad NFE

AF:

0.688

Gnomad OTH

AF:

0.682

GnomAD4 exome

AF:

0.784

AC:

116

AN:

148

Hom.:

Cov.:

AF XY:

0.773

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.804

AC:

111

AN:

138

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.375

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.563

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.683

AC:

103854

AN:

152046

Hom.:

35420

Cov.:

AF XY:

0.685

AC XY:

50910

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.679

AC:

28167

AN:

41464

American (AMR)

AF:

0.631

AC:

9642

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.671

AC:

2329

AN:

3472

East Asian (EAS)

AF:

0.729

AC:

3765

AN:

5168

South Asian (SAS)

AF:

0.631

AC:

3043

AN:

4820

European-Finnish (FIN)

AF:

0.776

AC:

8198

AN:

10564

Middle Eastern (MID)

AF:

0.602

AC:

177

AN:

294

European-Non Finnish (NFE)

AF:

0.688

AC:

46762

AN:

67978

Other (OTH)

AF:

0.676

AC:

1426

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1752

3504

5257

7009

8761

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

822

1644

2466

3288

4110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.678

Hom.:

94917

Bravo

AF:

0.667

Asia WGS

AF:

0.693

AC:

2412

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

(source)

DANN

Benign

0.69

PhyloP100

0.55

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over